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The advent of
digital
microscopy
Yves Sucaet,
Wim Waelput,
Peter In’t Veld
Biology edition 
14-11-2016 pag. 2
Financial disclosure
• Yves Sucaet and Wim Waelput are co-founders and
shareholders in Pathomation, an innovative company founded
in 2012. The company strives to offer the most
comprehensive software platform for digital pathology
possible. The focus is on integration, scalability, and user-
friendliness. Pathomation implements digital pathology in a
variety of use cases and scenarios.
14-11-2016 pag. 3
Prelude
• In October 2016, I was honored at Troy University as one of
its 2016 “alumni of the year” during the annual homecoming
activities.
• In the following week, I gave several guest lectures in various
departments across campus.
• This is the lecture as presented for the biology department on
Monday, October 17, 2016.
14-11-2016 pag. 4
Topics for today
• How did I get here?
• Digital microscopy
• Digital pathology
• Companion diagnostics
PERSONAL BACKGROUND
14-11-2016 pag. 6
Who am I (education)?
• 1998-2000: Hogeschool Gent (BE)
– BS Computer Sciences
• 2001-2005: Troy State University (US)
– Exchange program
• Developed an interest in using ComS to help (molecular) biologists
– MS Biological Sciences
• Research in yeast genetics with Dr. Christi Magrath (NSF fellowship)
• 2005-2010: Iowa State University
– PhD Bioinformatics & Computational Biology
Education
14-11-2016 pag. 7
Who am I (professional)
Professional
• 2000-2001: Becton Dickinson
• 2010-2013: HistoGeneX
• Section head Data Management & Bioinformatics
• 2012-now: Pathomation
• Chief Technology Officer
• 2014-Q1 2017: VUB
• Digital Pathology Manager
• 2016-now: HistoGeneX
• Data scientist
WHAT IS DIGITAL MICROSCOPY?
14-11-2016 pag. 9
This is not it
14-11-2016 pag. 10
Digital microscopy on a budget
14-11-2016 pag. 11
Add a camera “port”
14-11-2016 pag. 12
Add more automation
14-11-2016 pag. 13
Whole slide imaging (single slide)
14-11-2016 pag. 14
Whole slide imaging (clinical)
14-11-2016 pag. 15
WSI needs hardware and software
14-11-2016 pag. 16
Hardware
14-11-2016 pag. 17
Software
Very
large
image!
14-11-2016 pag. 18
How big are these images?
14-11-2016 pag. 19
When you get someone to scan your slides…
Enhanced network
infrastructure
I gave you slides;
how do I get to
see these?
14-11-2016 pag. 20
You have a hard time getting them back!
• You go to a website
• You download a .sis-file
• Which is not recognized by your browser
• Then you go to the scanner vendor’s website
• You download their free (but proprietary) viewer
• You install the viewer (do you have rights to do that?)
• You re-download the .sis-file
• You open the .sis-file in the locally installed viewer
• Sometimes the viewer is unstable and crashes
– that’s normal; just start over
• Re-do this procedure on every device that you use
– You just can’t do it on a Mac!
14-11-2016 pag. 21
Confusing your end-users (customers)! NOT good!
14-11-2016 pag. 22
Confusing your end-users (customers)! NOT good!
14-11-2016 pag. 23
What’s the solution?
14-11-2016 pag. 24
Digital microscopy at the VUB
14-11-2016 pag. 25
What does the Pathomation software look like?
(DIGITAL) PATHOLOGY 101
14-11-2016 pag. 27
What does a pathologist do?
14-11-2016 pag. 28
Tools for pathologists
14-11-2016 pag. 29
Digital tools for pathologists
14-11-2016 pag. 30
Digital (r)evolution
COMPANION DIAGNOSTICS
14-11-2016 pag. 32
The cost of cancer drugs
14-11-2016 pag. 33
How do cancer drugs work?
• Rituximab, Rituxan:
– monoclonal Ab that attacks CD20+ B cells
– Leukemia, lymphoma
• Trastuzumab, Herceptin
– Interferes with Her2/Neu receptor
– Breast cancer
• Imatinib, Gleevec
– Tyrosine Kinase Inhibitor
– Chronic Myelogenous Leukemia (CML), Gastrointestinal
tumors (GITs)
• Everolimus, Afinitor
– HR+ (ER or PR), Her2 negative
– Breast cancer
14-11-2016 pag. 34
To prescribe or not to prescribe?
• Expensive drugs only work in a subset of patients
– Herceptin: 20-30% of early stage breast cancer
• Only to be used in HER2/Neu positive patients
• Cost: $4,659 / month
– Affinitor: 35% of patients respond
• Only to be used in Her2 negative, HR positive patients
• Cost: $8,701 / month
– Ibrance:
• Only to be used in ER positive, Her2 negative
• Also for metastatic cancer
• Cost: $10,677 / month
– Avastin + Erbitux
• Triple Negative Breast Cancer (TNBC)
• Cost: $5,551 + $11,862
14-11-2016 pag. 35
The need for personalized medicine
Cancer
therapy
Resection
Radio
therapy
Targeted
Immune
therapy
Research
Chemot
herapy
% patients responding: 25%
20-30% patients benefits
from ipilimumab
Epigenetics
Combinations
Lung cancer :
EGFR - gefitinib
ALK - crizotinib
14-11-2016 pag. 36
So what do you do?
• Companion diagnostics are tests that are administered to assess
what treatment is suited for a particular patient
– Can save lots of resources (time, money), and therefore
lives
– cDX is usually done on a (liquid) biopsy or resection
• Which means a pathologist is involved
– Allows clinician to take shortcuts!
• Sometimes a 3rd line treatment can be opted for directly as a 1st
line treatment
– Paves the way for personalized medicine
• Get the right drug to the right patient at the right time
• (at the right price for the patient and for society)
14-11-2016 pag. 37
A breast cancer panel
• Immunohistochemical stains
– Assess the presence of specific molecules (proteins) in cells
(see Dr. Cohen for more info  )
– E-CAD: loss of E-cadherin function is often associated with
tumor progression and transition to more invasive disease
– Ki67: aggressiveness (assess speed of cell division)
– Hormone Receptors (Progesterone, Estrogen)
– HER2/Nue Receptor
• See http://histosrv.vub.ac.be/cases2/scen03/#0,3
• See http://histosrv.vub.ac.be/cases2/scen03/#8,18
• Determine the therapy based on the outcome of the various
immunohistochemical stains
14-11-2016 pag. 38
How can digital microscopy help?
• In the future: Automatic assessment of stained slides
– Decision support systems
– Most importantly: help troubleshoot borderline
cases!
• Today: Training the pathologist for make the right assessment
– http://training.Pathomation.com
• Today: Facilitate discussion
– Tumor boards, multidisciplinary oncological consults
– Second opinions
14-11-2016 pag. 39
The stakes are high!
128B market cap / 83B market cap
IN CLOSING
14-11-2016 pag. 41
Conclusions
• Digital pathology is ready for prime time
– Education and training,
– Research (including biobanking)
• DIY digital pathology
– Do your due diligence: hardware AND software
– DON’T spend all your resources on “stuff”
• Hire the right people to implement the right workflows
– Start with one use case, expand to others
– Spread the word and share experiences
• Digital Pathology Association, International Academy of
Digital Pathology, European Society of Pathology…
14-11-2016 pag. 42
Learn more about digital pathology
14-11-2016 pag. 43
Continue the conversation
• Email: yves.sucaet@gmail.com
Thank you for inviting me!

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The Troy lectures: The advent of digital microscopy (biology edition)

  • 1. The advent of digital microscopy Yves Sucaet, Wim Waelput, Peter In’t Veld Biology edition 
  • 2. 14-11-2016 pag. 2 Financial disclosure • Yves Sucaet and Wim Waelput are co-founders and shareholders in Pathomation, an innovative company founded in 2012. The company strives to offer the most comprehensive software platform for digital pathology possible. The focus is on integration, scalability, and user- friendliness. Pathomation implements digital pathology in a variety of use cases and scenarios.
  • 3. 14-11-2016 pag. 3 Prelude • In October 2016, I was honored at Troy University as one of its 2016 “alumni of the year” during the annual homecoming activities. • In the following week, I gave several guest lectures in various departments across campus. • This is the lecture as presented for the biology department on Monday, October 17, 2016.
  • 4. 14-11-2016 pag. 4 Topics for today • How did I get here? • Digital microscopy • Digital pathology • Companion diagnostics
  • 6. 14-11-2016 pag. 6 Who am I (education)? • 1998-2000: Hogeschool Gent (BE) – BS Computer Sciences • 2001-2005: Troy State University (US) – Exchange program • Developed an interest in using ComS to help (molecular) biologists – MS Biological Sciences • Research in yeast genetics with Dr. Christi Magrath (NSF fellowship) • 2005-2010: Iowa State University – PhD Bioinformatics & Computational Biology Education
  • 7. 14-11-2016 pag. 7 Who am I (professional) Professional • 2000-2001: Becton Dickinson • 2010-2013: HistoGeneX • Section head Data Management & Bioinformatics • 2012-now: Pathomation • Chief Technology Officer • 2014-Q1 2017: VUB • Digital Pathology Manager • 2016-now: HistoGeneX • Data scientist
  • 8. WHAT IS DIGITAL MICROSCOPY?
  • 10. 14-11-2016 pag. 10 Digital microscopy on a budget
  • 11. 14-11-2016 pag. 11 Add a camera “port”
  • 12. 14-11-2016 pag. 12 Add more automation
  • 13. 14-11-2016 pag. 13 Whole slide imaging (single slide)
  • 14. 14-11-2016 pag. 14 Whole slide imaging (clinical)
  • 15. 14-11-2016 pag. 15 WSI needs hardware and software
  • 18. 14-11-2016 pag. 18 How big are these images?
  • 19. 14-11-2016 pag. 19 When you get someone to scan your slides… Enhanced network infrastructure I gave you slides; how do I get to see these?
  • 20. 14-11-2016 pag. 20 You have a hard time getting them back! • You go to a website • You download a .sis-file • Which is not recognized by your browser • Then you go to the scanner vendor’s website • You download their free (but proprietary) viewer • You install the viewer (do you have rights to do that?) • You re-download the .sis-file • You open the .sis-file in the locally installed viewer • Sometimes the viewer is unstable and crashes – that’s normal; just start over • Re-do this procedure on every device that you use – You just can’t do it on a Mac!
  • 21. 14-11-2016 pag. 21 Confusing your end-users (customers)! NOT good!
  • 22. 14-11-2016 pag. 22 Confusing your end-users (customers)! NOT good!
  • 24. 14-11-2016 pag. 24 Digital microscopy at the VUB
  • 25. 14-11-2016 pag. 25 What does the Pathomation software look like?
  • 27. 14-11-2016 pag. 27 What does a pathologist do?
  • 28. 14-11-2016 pag. 28 Tools for pathologists
  • 29. 14-11-2016 pag. 29 Digital tools for pathologists
  • 32. 14-11-2016 pag. 32 The cost of cancer drugs
  • 33. 14-11-2016 pag. 33 How do cancer drugs work? • Rituximab, Rituxan: – monoclonal Ab that attacks CD20+ B cells – Leukemia, lymphoma • Trastuzumab, Herceptin – Interferes with Her2/Neu receptor – Breast cancer • Imatinib, Gleevec – Tyrosine Kinase Inhibitor – Chronic Myelogenous Leukemia (CML), Gastrointestinal tumors (GITs) • Everolimus, Afinitor – HR+ (ER or PR), Her2 negative – Breast cancer
  • 34. 14-11-2016 pag. 34 To prescribe or not to prescribe? • Expensive drugs only work in a subset of patients – Herceptin: 20-30% of early stage breast cancer • Only to be used in HER2/Neu positive patients • Cost: $4,659 / month – Affinitor: 35% of patients respond • Only to be used in Her2 negative, HR positive patients • Cost: $8,701 / month – Ibrance: • Only to be used in ER positive, Her2 negative • Also for metastatic cancer • Cost: $10,677 / month – Avastin + Erbitux • Triple Negative Breast Cancer (TNBC) • Cost: $5,551 + $11,862
  • 35. 14-11-2016 pag. 35 The need for personalized medicine Cancer therapy Resection Radio therapy Targeted Immune therapy Research Chemot herapy % patients responding: 25% 20-30% patients benefits from ipilimumab Epigenetics Combinations Lung cancer : EGFR - gefitinib ALK - crizotinib
  • 36. 14-11-2016 pag. 36 So what do you do? • Companion diagnostics are tests that are administered to assess what treatment is suited for a particular patient – Can save lots of resources (time, money), and therefore lives – cDX is usually done on a (liquid) biopsy or resection • Which means a pathologist is involved – Allows clinician to take shortcuts! • Sometimes a 3rd line treatment can be opted for directly as a 1st line treatment – Paves the way for personalized medicine • Get the right drug to the right patient at the right time • (at the right price for the patient and for society)
  • 37. 14-11-2016 pag. 37 A breast cancer panel • Immunohistochemical stains – Assess the presence of specific molecules (proteins) in cells (see Dr. Cohen for more info  ) – E-CAD: loss of E-cadherin function is often associated with tumor progression and transition to more invasive disease – Ki67: aggressiveness (assess speed of cell division) – Hormone Receptors (Progesterone, Estrogen) – HER2/Nue Receptor • See http://histosrv.vub.ac.be/cases2/scen03/#0,3 • See http://histosrv.vub.ac.be/cases2/scen03/#8,18 • Determine the therapy based on the outcome of the various immunohistochemical stains
  • 38. 14-11-2016 pag. 38 How can digital microscopy help? • In the future: Automatic assessment of stained slides – Decision support systems – Most importantly: help troubleshoot borderline cases! • Today: Training the pathologist for make the right assessment – http://training.Pathomation.com • Today: Facilitate discussion – Tumor boards, multidisciplinary oncological consults – Second opinions
  • 39. 14-11-2016 pag. 39 The stakes are high! 128B market cap / 83B market cap
  • 41. 14-11-2016 pag. 41 Conclusions • Digital pathology is ready for prime time – Education and training, – Research (including biobanking) • DIY digital pathology – Do your due diligence: hardware AND software – DON’T spend all your resources on “stuff” • Hire the right people to implement the right workflows – Start with one use case, expand to others – Spread the word and share experiences • Digital Pathology Association, International Academy of Digital Pathology, European Society of Pathology…
  • 42. 14-11-2016 pag. 42 Learn more about digital pathology
  • 43. 14-11-2016 pag. 43 Continue the conversation • Email: yves.sucaet@gmail.com Thank you for inviting me!